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C60 Fullerene Governs Doxorubicin Effect on Metabolic Profile of Rat Microglial Cells In Vitro.
Molecular Pharmaceutics ( IF 4.9 ) Pub Date : 2020-07-16 , DOI: 10.1021/acs.molpharmaceut.0c00691
Yevheniia Hurmach 1 , Mariia Rudyk 2 , Svitlana Prylutska 2 , Vasyl Hurmach 2 , Yuriy I Prylutskyy 2 , Uwe Ritter 3 , Peter Scharff 3 , Larysa Skivka 2
Affiliation  

Background: C60 fullerenes and their derivatives are actively investigated for the use in neuroscience. Applications of these nanoscale materials require the examination of their interaction with different neural cells, especially with microglia, because these cells, like other tissue resident phagocytes, are the earliest and most sensitive responders to nanoparticles. The aim of this study was to investigate the effect of C60 fullerene and its nanocomplex with doxorubicin (Dox) on the metabolic profile of brain-resident phagocytes—microglia—in vitro. Methods: Resting microglial cells from adult male Wistar rats were used in experiments. Potential C60 fullerene targets in microglial cells were studied by computer simulation. Microglia oxidative metabolism and phagocytic activity were examined by flow cytometry. Griess reaction and arginase activity colorimetric assay were used to explore arginine metabolism. Results: C60 fullerene when used alone did not influence microglia oxidative metabolism and phagocytic activity but shifted arginine metabolism toward the decrease of NO generation. Complexation of C60 fullerene with Dox (C60–Dox) potentiated the ability of the latter to stimulate NO generation. Conclusion: The capability of C60 fullerenes used alone to cause anti-inflammatory shift of microglia arginine metabolism makes them a promising agent for the correction of neuroinflammatory processes involved in neurodegeneration. The potentiating action of C60 fullerene on the immunomodulatory effect of Dox allows us to consider the C60 molecule as an attractive vehicle for this antitumor agent.

中文翻译:

C60富勒烯在体外控制阿霉素对大鼠小胶质细胞代谢谱的影响。

背景:人们正在积极研究C 60富勒烯及其衍生物在神经科学中的用途。这些纳米级材料的应用需要检查它们与不同神经细胞(特别是与小胶质细胞)的相互作用,因为这些细胞像其他组织驻留吞噬细胞一样,是对纳米粒子的最早且最敏感的反应器。这项研究的目的是研究C 60富勒烯及其与阿霉素(Dox)的纳米复合物在体外对大脑驻留吞噬细胞(小胶质细胞)代谢谱的影响。方法:使用成年雄性Wistar大鼠的静止小胶质细胞进行实验。电位C 60通过计算机模拟研究了小胶质细胞中的富勒烯靶标。通过流式细胞术检查小胶质细胞的氧化代谢和吞噬活性。用Griess反应和精氨酸酶活性比色法研究了精氨酸的代谢。结果:单独使用时,C 60富勒烯不会影响小胶质细胞的氧化代谢和吞噬活性,但会导致精氨酸代谢向NO生成量的减少转移。C 60富勒烯与Dox(C 60 –Dox)的络合增强了后者刺激NO生成的能力。结论:C 60的能力富勒烯单独用于引起小胶质细胞精氨酸代谢的消炎转变,使其成为纠正与神经变性有关的神经炎症过程的有前途的药物。C 60富勒烯对Dox免疫调节作用的增强作用使我们可以考虑将C 60分子作为该抗肿瘤剂的有吸引力的载体。
更新日期:2020-09-09
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